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• W2081132593 abstract "We have previously shown that stimulation of striatal D1 receptors affects dopaminergic nigrostriatal terminal excitability, which is thought to be an index of biophysical events resulting from the activation of receptors on the presynaptic membrane. The experiments presented here further examine the locus and bases of these D1 effects in the rat. We now report that striatal administration of the D1 receptor selective antagonist R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazapine-7-ol-HCl (SCH 23390) produces a paradoxical agonist-like decrease in dopaminergic terminal excitability. This effect is blocked by pretreatment with the dopamine synthesis inhibitor, alpha-methyl-paratyrosine, suggesting that the action of SCH 23390 is dependent upon endogenous dopamine. Further, haloperidol pretreatment also prevents the SCH 23390-induced decrease in terminal excitability, confirming that dopamine, acting through a dopamine receptor, is responsible for this agonist-like action. Striatal application of the active R-(+) enantiomer of the dopaminergic D1-selective agonist 1-phenyl-2,3,4,5-tetrahydrol-(1H)-3-benzazepine-7, 8-diol-HCl (R-SKF 38393) decreases terminal excitability in the alphamethyl-paratyrosine pretreated animal, indicating that dopamine is not required for the agonist action. In an effort to ascertain the presynaptic or postsynaptic location of these actions, an extensive destruction of postsynaptic neurons in the neostriatum was produced by local administration of the neurotoxin, kainic acid. It was observed that the neurotoxin-induced neostriatal neuronal loss did not disrupt the action of R-SKF 38393 nor its reversal by SCH 23390. Finally, to exclude the possibility that R-SKF 38393 may act through a D2 receptor, an additional group of animals was pretreated with the D2-selective antagonist, (−)-sulpiride. The D1-selective agonist still decreased excitability following this pretreatment, indicating that the agonist action is not mediated through D2 receptors." @default.
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• W2081132593 date "1991-01-01" @default.
• W2081132593 modified "2023-10-16" @default.
• W2081132593 title "Modulation of dopaminergic terminal excitability by D1 selective agents: Further characterization" @default.
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• W2081132593 doi "https://doi.org/10.1016/0306-4522(91)90387-4" @default.
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